Daniel R. Bauer

Microwave-Induced Thermoacoustic Imaging Model for Potential Breast Cancer Detection

In this study, we develop a complete microwave-induced thermoacoustic imaging (TAI) model for potential breast cancer imaging application. Acoustic pressures generated by different breast tissue targets are investigated by finite-difference time-domain simulations of the entire TAI process including the feeding antenna, matching mechanism, fluidic environment, 3-D breast model, and acoustic transducer. Simulation results achieve quantitative relationships between the input microwave peak power and the resulting specific absorption rate as well as the output acoustic pressure. Microwave frequency dependence of the acoustic signals due to different breast tissues is established across a broadband frequency range (2.3-12 GHz), suggesting key advantages of spectroscopic TAI compare to TAI at a single frequency. Reconstructed thermoacoustic images are consistent with the modeling results. This model will contribute to design, optimization, and safety evaluation of microwave-induced TAI and spectroscopy.

Real-time photoacoustic and ultrasound imaging: a simple solution for clinical ultrasound systems with linear arrays

Recent clinical studies have demonstrated that photoacoustic imaging (PAI) provides important diagnostic information during a routine breast exam for cancer. PAI enhances contrast between blood vessels and background tissue, which can help characterize suspicious lesions. However, most PAI systems are either not compatible with commercial ultrasound systems or inefficiently deliver light to the region of interest, effectively reducing the sensitivity of the technique. To address and potentially overcome these limitations, we developed an accessory for a standard linear ultrasound array that optimizes light delivery for PAI. The photoacoustic enabling device (PED) exploits an optically transparent acoustic reflector to help direct laser illumination to the region of interest. This study compares the PED with standard fiber bundle illumination in scattering and non-scattering media. In scattering media with the same incident fluence, the PED enhanced the photoacoustic signal by 18 dB at a depth of 5 mm and 6 dB at a depth of 20 mm. To demonstrate in vivo feasibility, we also used the device to image a mouse with a pancreatic tumor. The PED identified blood vessels at the periphery of the tumor, suggesting that PAI provides complementary contrast to standard pulse echo ultrasound. The PED is a simple and inexpensive solution that facilitates the translation of PAI technology to the clinic for routine screening of breast cancer.

Real-time, contrast enhanced photoacoustic imaging of cancer in a mouse window chamber.

A clinical ultrasound scanner and 14 MHz linear array collected real-time photoacoustic images (PAI) during an injection of gold nanorods (GNRs) near the region of a mature PC-3 prostate tumor in mice implanted with a skin flap window chamber. Three dimensional spectroscopic PAI (690-900 nm) was also performed to investigate absorption changes near the tumor and enhance specific detection of GNRs. Whereas GNRs improved PAI contrast (+18 dB), the photoacoustic spectrum was consistent with the elevated near infrared absorption of GNRs. The versatile imaging platform potentially accelerates development of photoacoustic contrast agents and drug delivery for cancer imaging and therapy.

Spectroscopic thermoacoustic imaging of water and fat composition

During clinical studies, thermoacoustic imaging (TAI) failed to reliably identify malignant breast tissue. To increase detection capability, we propose spectroscopic TAI to differentiate samples based on the slope of their dielectric absorption. Phantoms composed of different ratios of water and fat were imaged using excitation frequencies between 2.7 and 3.1 GHz. The frequency-dependent slope of the TA signal was highly correlated with that of its absorption coefficient (R2 = 0.98 and p < 0.01), indicating spectroscopic TAI can distinguish materials based on their intrinsic dielectric properties. This approach potentially enhances cancer detection due to the increased water content of many tumors.

3-D photoacoustic and pulse echo imaging of prostate tumor progression in the mouse window chamber

Understanding the tumor microenvironment is critical to characterizing how cancers operate and predicting their response to treatment. We describe a novel, high-resolution coregistered photoacoustic (PA) and pulse echo (PE) ultrasound system used to image the tumor microenvironment. Compared to traditional optical systems, the platform provides complementary contrast and important depth information. Three mice are implanted with a dorsal skin flap window chamber and injected with PC-3 prostate tumor cells transfected with green fluorescent protein. The ensuing tumor invasion is mapped during three weeks or more using simultaneous PA and PE imaging at 25 MHz, combined with optical and fluorescent techniques. Pulse echo imaging provides details of tumor structure and the surrounding environment with 100-μm(3) resolution. Tumor size increases dramatically with an average volumetric growth rate of 5.35 mm(3)/day, correlating well with 2-D fluorescent imaging (R = 0.97, p < 0.01). Photoacoustic imaging is able to track the underlying vascular network and identify hemorrhaging, while PA spectroscopy helps classify blood vessels according to their optical absorption spectrum, suggesting variation in blood oxygen saturation. Photoacoustic and PE imaging are safe, translational modalities that provide enhanced depth resolution and complementary contrast to track the tumor microenvironment, evaluate new cancer therapies, and develop molecular contrast agents in vivo.

Impact of Microwave Pulses on Thermoacoustic Imaging Applications

Thermoacoustic imaging is a promising modality for breast cancer detection. Acoustic signals generated by tumor targets with different sizes subject to microwave pulses with various widths and waveforms are analytically studied in this letter. Time- and frequency-domain profiles of the acoustic signals are achieved. Some key parameters of the acoustic signals, including peak value and peak-to-peak time interval of the time-domain acoustic pressure and frequency of the global peak and magnitude ratio of the second highest peak to the global peak of the frequency-domain pressure, are discussed. Impact of pulse width on acoustic signal peak-to-peak interval and image spatial resolution is developed. Square pulse is demonstrated to be superior in acquiring higher image resolution and signal-to-noise ratio. This study is helpful to optimizing the microwave pulse, selecting acoustic transducer, and evaluating image resolution.

In vivo multi-modality photoacoustic and pulse echo tracking of prostate tumor growth using a window chamber

Understanding the tumor microenvironment is critical to characterizing how cancers operate and predicting how they will eventually respond to treatment. The mouse window chamber model is an excellent tool for cancer research, because it enables high resolution tumor imaging and cross-validation using multiple modalities. We describe a novel multimodality imaging system that incorporates three dimensional (3D) photoacoustics with pulse echo ultrasound for imaging the tumor microenvironment and tracking tissue growth in mice. Three mice were implanted with a dorsal skin flap window chamber. PC-3 prostate tumor cells, expressing green fluorescent protein (GFP), were injected into the skin. The ensuing tumor invasion was mapped using photoacoustic and pulse echo imaging, as well as optical and fluorescent imaging for comparison and cross validation. The photoacoustic imaging and spectroscopy system, consisting of a tunable (680-1000nm) pulsed laser and 25 MHz ultrasound transducer, revealed near infrared absorbing regions, primarily blood vessels. Pulse echo images, obtained simultaneously, provided details of the tumor microstructure and growth with 100-μm3 resolution. The tumor size in all three mice increased between three and five fold during 3+ weeks of imaging. Results were consistent with the optical and fluorescent images. Photoacoustic imaging revealed detailed maps of the tumor vasculature, whereas photoacoustic spectroscopy identified regions of oxygenated and deoxygenated blood vessels. The 3D photoacoustic and pulse echo imaging system provided complementary information to track the tumor microenvironment, evaluate new cancer therapies, and develop molecular imaging agents in vivo. Finally, these safe and noninvasive techniques are potentially applicable for human cancer imaging.

Microwave induced thermal acoustic imaging modeling for potential breast cancer detection

In this work, we develop a complete microwave induced thermal acoustic imaging (TAI) model for potential biomedical imaging applications. Acoustic pressure generated by spherical breast tumor target is investigated by finite-difference time-domain (FDTD) simulations of the electromagnetic (EM) and acoustic models. Simulation results achieve quantitative relationship between the input power and the output acoustic pressure. Microwave frequency dependence of the acoustic pressure is established in a broadband frequency range. This model will enable design and optimization of microwave induced thermal acoustic imaging and spectroscopy.

Computational study of thermoacoustic imaging for breast cancer detection using a realistic breast model

The effectiveness of thermoacoustic imaging (TAI) for breast cancer detection is demonstrated by a computational study using a realistic breast model. Carbon nanotubes are applied as contrast agents to enhance the detectability of breast tumors. Differential imaging is performed to visualize the tumor. The position, dimension and morphology of the tumor are all reliably reconstructed in the differential image. This work provides a sub-stantial evidence of the advantages of TAI as a potential breast cancer detection modality.

A hybrid microwave / acoustic communication scheme — Thermoacoustic communication

A hybrid wireless communication approach, thermoacoustic communication (TAC), is introduced. Based on thermoacoustic effect, TAC is able to directly convert electromagnetic energy into acoustic energy without involving any intermediate device. Detailed description of TAC working principles is provided. A proof-of-concept experiment is performed to demonstrate the TAC concept.